The diagnosis, and thus therapy, of solid tumors of childhood is often difficult due to lack of distinguishing characteristics. This is especially true of Ewing's sarcoma, neuroblastoma, primitive soft tissue sarcomas, and (occasionally) lymphoma. We have evaluated the presence of a specific neural enzyme, neuron-specific enolase (NSE), in paraffin-embedded sections of a diverse group of solid childhood tumors, including previously unrecognized variants of neural tumors, employing immunocytochemistry with antisera to NSE. We find uniform reactivity of all neural tumors with this antibody. No cross reactivity with non-neural tumors, save a rare example of differentiated rhabdomyosarcoma, was found. We conclude that NSE is a reliable, readily detected marker in even primitive childhood tumors of neural origin. Since these tumors, in particular, appear to have an ominous prognosis outside the neonatal age group, recognition is especially important for therapeutic and prognostic purposes.